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Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling

Author

Listed:
  • Brian D. Robinson

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine)

  • Panagiotis J. Vlachostergios

    (Weill Cornell Medicine)

  • Bhavneet Bhinder

    (Weill Cornell Medicine
    Weill Cornell Medicine)

  • Weisi Liu

    (Weill Cornell Medicine)

  • Kailyn Li

    (Weill Cornell Medicine)

  • Tyler J. Moss

    (The University of Texas MD Anderson Cancer Center)

  • Rohan Bareja

    (Weill Cornell Medicine
    Weill Cornell Medicine)

  • Kyung Park

    (Weill Cornell Medicine)

  • Peyman Tavassoli

    (Weill Cornell Medicine)

  • Joanna Cyrta

    (Weill Cornell Medicine
    Weill Cornell Medicine)

  • Scott T. Tagawa

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine
    Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine)

  • David M. Nanus

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine
    Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine)

  • Himisha Beltran

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine
    Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine)

  • Ana M. Molina

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine
    Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine)

  • Francesca Khani

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine)

  • Juan Miguel Mosquera

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine)

  • Evanguelos Xylinas

    (Weill Cornell Medicine
    Paris Descartes University)

  • Shahrokh F. Shariat

    (Weill Cornell Medicine
    Medical University of Vienna)

  • Douglas S. Scherr

    (Weill Cornell Medicine)

  • Mark A. Rubin

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine
    Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine)

  • Seth P. Lerner

    (Baylor College of Medicine)

  • Surena F. Matin

    (The University of Texas MD Anderson Cancer Center)

  • Olivier Elemento

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine
    Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine)

  • Bishoy M. Faltas

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine
    Weill Cornell Medicine)

Abstract

Upper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis of whole-exome and RNA sequencing of UTUC. Here we report several key insights from our molecular dissection of this disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has a T-cell depleted immune contexture; 3) High FGFR3 expression is enriched in UTUC and correlates with its T-cell depleted immune microenvironment; 4) Sporadic UTUC is characterized by a lower total mutational burden than urothelial carcinoma of the bladder. Our findings lay the foundation for a deeper understanding of UTUC biology and provide a rationale for the development of UTUC-specific treatment strategies.

Suggested Citation

  • Brian D. Robinson & Panagiotis J. Vlachostergios & Bhavneet Bhinder & Weisi Liu & Kailyn Li & Tyler J. Moss & Rohan Bareja & Kyung Park & Peyman Tavassoli & Joanna Cyrta & Scott T. Tagawa & David M. N, 2019. "Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10873-y
    DOI: 10.1038/s41467-019-10873-y
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    Cited by:

    1. Michiel S. Heijden & Thomas Powles & Daniel Petrylak & Ronald Wit & Andrea Necchi & Cora N. Sternberg & Nobuaki Matsubara & Hiroyuki Nishiyama & Daniel Castellano & Syed A. Hussain & Aristotelis Bamia, 2022. "Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Kentaro Ohara & André Figueiredo Rendeiro & Bhavneet Bhinder & Kenneth Wha Eng & Hiranmayi Ravichandran & Duy Nguyen & David Pisapia & Aram Vosoughi & Evan Fernandez & Kyrillus S. Shohdy & Jyothi Mano, 2024. "The evolution of metastatic upper tract urothelial carcinoma through genomic-transcriptomic and single-cell protein markers analysis," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. A. Gordon Robertson & Khyati Meghani & Lauren Folgosa Cooley & Kimberly A. McLaughlin & Leigh Ann Fall & Yanni Yu & Mauro A. A. Castro & Clarice S. Groeneveld & Aurélien Reyniès & Vadim I. Nazarov & V, 2023. "Expression-based subtypes define pathologic response to neoadjuvant immune-checkpoint inhibitors in muscle-invasive bladder cancer," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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